, Inhaled corticosteroids; LABA, Long-acting beta2-agonists; LTRA, Leukotriene receptor antagonists; OCS, Oral corticosteroids, ICS, vol.SABA

, subjects never or irregularly exposed to ICS (i.e., <6months/year) between EGEA1 and 2; ICS++, subjects regularly or continuously exposed to ICS (i.e., ?6 months/year), ICS

, Education Nationale; ICS, inhaled corticosteroids; LTRA, leukotriene receptor antagonists; SABA, short acting beta 2 -agonists. Impact of " Pharmacome

S. Chanoine, P. D. , M. Sanchez, S. Temam, and M. Sc, Agnès Fournier, Ph.D. Isabelle Pin, M.D. 1 Ph.D. Gianluca Severi, Ph.D. Jean Bousquet, M.D. Pierrick Bedouch, Pharm.D, vol.67287121314715165172, issue.43, 2005.

I. and I. , Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, F-38000 Grenoble

, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, p.38000

A. Chu-grenoble, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, p.38000

P. Pharmacie and . Chu-grenoble-alpes,

, Aging and chronic diseases, Epidemiological and public health approaches

, Quentin-en-Yvelines, UMRS-S 1168, F-78180

C. Clinique-de-pédiatrie and . Grenoble,

, France 10 INSERM, Center for research in Epidemiology and Population Health (CESP), UMRS 1018, Health across generation team, F-94807, 11 Human Genetics Foundation (HuGeF), p.12

C. Universitaire-de-pneumologie, P. Thorax, . Vaisseaux, and . Chu-grenoble-alpes, Contre les Maladies Chroniques pour un VIeillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site

S. Wenzel, Asthma: defining of the persistent adult phenotypes, The Lancet, vol.368, issue.9537, pp.804-817, 2006.
DOI : 10.1016/S0140-6736(06)69290-8

, Global Initiative for Asthma Global Strategy for Asthma Management and Prevention. www.ginasthma.org. Date last updated: 2016. Date last accessed, 2016.

D. Postma and K. Rabe, The Asthma???COPD Overlap Syndrome, New England Journal of Medicine, vol.373, issue.13, pp.1241-1250, 2015.
DOI : 10.1056/NEJMra1411863

, Global Initiative for Asthma and Global Initiative for Chronic Obstructive Disease Diagnosis of diseases of chronic airflow limitations: Asthma, COPD and Asthma-COPD overlap syndrome (ACOS). www.ginasthma.org. Date last updated: 2015. Date last accessed, 2016.

R. Nathan, C. Sorkness, M. Kosinski, M. Schatz, J. Li et al., Development of the asthma control test???A survey for assessing asthma control, Journal of Allergy and Clinical Immunology, vol.113, issue.1, pp.59-65, 2004.
DOI : 10.1016/j.jaci.2003.09.008

B. Lambrecht and H. Hammad, The airway epithelium in asthma, Nature Medicine, vol.184, issue.5, pp.684-92, 2012.
DOI : 10.1164/rccm.201101-0106OC

O. Byrne, P. Pedersen, S. Lamm, C. Tan, W. Busse et al., Severe Exacerbations and Decline in Lung Function in Asthma, American Journal of Respiratory and Critical Care Medicine, vol.179, issue.1, pp.19-24, 2009.
DOI : 10.1056/NEJM199711133372001

K. Torén, J. Brisman, and B. Järvholm, Asthma and Asthma-like Symptoms in Adults Assessed by Questionnaires, Chest, vol.104, issue.2, pp.600-608, 1993.
DOI : 10.1378/chest.104.2.600

B. Ferris, Epidemiology Standardization Project Am Rev Respir Dis. Pt, vol.118, issue.2, pp.1-120, 1978.

P. Burney, L. Laitinen, S. Perdrizet, H. Huckauf, A. Tattersfield et al., Validity and repeatability of the IUATLD (1984) Bronchial Symptoms Questionnaire: an international comparison, Eur Respir J, vol.2, issue.10, pp.940-945, 1989.

M. Sanchez, R. Varraso, J. Bousquet, F. Clavel-chapelon, C. Pison et al., Perceived 10-year change in respiratory health: Reliability and predictive ability, Respiratory Medicine, vol.109, issue.2, pp.188-99, 2015.
DOI : 10.1016/j.rmed.2014.11.010
URL : https://hal.archives-ouvertes.fr/hal-01969368

M. Grassi, S. Villani, and A. Marinoni, European Community Respiratory Health Survey Group. Classification methods for the identification of 'case' in epidemiological diagnosis of asthma

, Eur J Epidemiol, vol.17, issue.1, pp.19-29, 2001.

J. Pekkanen, J. Sunyer, J. Anto, and P. Burney, Operational definitions of asthma in studies on its aetiology, European Respiratory Journal, vol.26, issue.1, pp.28-35, 2005.
DOI : 10.1183/09031936.05.00120104

J. Sunyer, J. Pekkanen, R. Garcia-esteban, C. Svanes, N. Künzli et al., Asthma score: predictive ability and risk factors, Allergy, vol.171, issue.2, pp.142-150, 2007.
DOI : 10.1164/rccm.200402-230OC

F. Kauffmann, M. Dizier, I. Annesi-maesano, J. Bousquet, D. Charpin et al., Epidemiological study of genetic and environmental factors in asthma, bronchial hyperresponsiveness and atopy. Protocol and potential selection bias], Rev Epidemiol Sante Publique, vol.49, issue.4, pp.343-56, 2001.
URL : https://hal.archives-ouvertes.fr/hal-00596430

M. Masoli, D. Fabian, S. Holt, and R. Beasley, Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee report

, Allergy, vol.59, issue.5, pp.469-78, 2004.

T. To, S. Stanojevic, G. Moores, A. Gershon, E. Bateman et al., Global asthma prevalence in adults: findings from the cross-sectional world health survey, BMC Public Health, vol.179, issue.5, p.204, 2012.
DOI : 10.1503/cmaj.081332

J. Bousquet, M. Ndiaye, N. Aït-khaled, I. Annesi-maesano, and A. Vignola, Management of chronic respiratory and allergic diseases in developing countries. Focus on sub-Saharan Africa, Allergy, vol.76, issue.4, pp.265-83, 2003.
DOI : 10.1136/oem.57.10.698
URL : https://hal.archives-ouvertes.fr/hal-00596421

W. Eder, M. Ege, and E. Von-mutius, The Asthma Epidemic, New England Journal of Medicine, vol.355, issue.21, pp.2226-2261, 2006.
DOI : 10.1056/NEJMra054308

S. Braman, The Global Burden of Asthma, Chest, vol.130, issue.1, pp.4-12, 2006.
DOI : 10.1378/chest.130.1_suppl.4S

O. Selroos, M. Kupczyk, P. Kuna, P. ?acwik, J. Bousquet et al., National and regional asthma programmes in Europe, European Respiratory Review, vol.24, issue.137, pp.474-83, 2015.
DOI : 10.1183/16000617.00008114

M. Delmas, C. Fuhrman, and S. Pour-le-groupe-Épidémiologie-et-recherche-clinique-de-la, L???asthme en France??: synth??se des donn??es ??pid??miologiques descriptives, Revue des Maladies Respiratoires, vol.27, issue.2, pp.151-160, 2010.
DOI : 10.1016/j.rmr.2009.09.001

T. To, S. Stanojevic, R. Feldman, R. Moineddin, E. Atenafu et al., Is asthma a vanishing disease? A study to forecast the burden of asthma in 2022, BMC Public Health, vol.129, issue.11, p.254, 2013.
DOI : 10.1016/j.jaci.2011.11.014

T. Eagan, J. Brøgger, G. Eide, and P. Bakke, The incidence of adult asthma: a review, Int J Tuberc Lung Dis, vol.9, issue.6, pp.603-615, 2005.

, Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries: a systematic analysis for the Global Burden of Disease Study, Global Burden of Disease Study 2013 Collaborators, 1990.

, Lancet, vol.386, issue.9995, pp.743-800, 2015.

, Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013, GBD 2013 Mortality and Causes of Death Collaborators, pp.117-71, 2015.

I. Torjesen, Two thirds of deaths from asthma are preventable, confidential inquiry finds, BMJ, vol.348, issue.may02 9, p.3108, 2014.
DOI : 10.1136/bmj.g3108

G. Gibson, R. Loddenkemper, B. Lundbäck, and Y. Sibille, Respiratory health and disease in Europe: the new European Lung White Book, European Respiratory Journal, vol.42, issue.3, pp.559-63, 2013.
DOI : 10.1183/09031936.00105513

. Ministère-de-l-'emploi, . De-la-solidarité-et-délégué-À-la, and . Santé, Programme d'actions, de prévention et de prise en charge de l'asthme 2002-2005, 2016.

M. Doz, C. Chouaid, L. Com-ruelle, E. Calvo, M. Brosa et al., The association between asthma control, health care costs, and quality of life in France and Spain, BMC Pulmonary Medicine, vol.45, issue.9, p.15, 2013.
DOI : 10.1080/02770900802216783

L. Cazzoletti, A. Marcon, C. Janson, A. Corsico, D. Jarvis et al., Asthma control in Europe: A real-world evaluation based on an international population-based study, Journal of Allergy and Clinical Immunology, vol.120, issue.6, pp.1360-1367, 2007.
DOI : 10.1016/j.jaci.2007.09.019
URL : https://hal.archives-ouvertes.fr/inserm-00348823

E. Van-ganse, L. Laforest, G. Pietri, J. Boissel, F. Gormand et al., Persistent asthma: disease control, resource utilisation and direct costs, European Respiratory Journal, vol.20, issue.2, pp.260-267, 2002.
DOI : 10.1183/09031936.02.02542001

M. Moffatt, I. Gut, F. Demenais, D. Strachan, E. Bouzigon et al., A Large-Scale, Consortium-Based Genomewide Association Study of Asthma, New England Journal of Medicine, vol.363, issue.13, pp.1211-1232, 2010.
DOI : 10.1056/NEJMoa0906312
URL : https://hal.archives-ouvertes.fr/inserm-00748663

Y. Zhang, M. Moffatt, and W. Cookson, Genetic and genomic approaches to asthma, Current Opinion in Pulmonary Medicine, vol.18, issue.1, pp.6-13, 2012.
DOI : 10.1097/MCP.0b013e32834dc532

C. Ober and T. Yao, The genetics of asthma and allergic disease: a 21st century perspective, Immunological Reviews, vol.127, issue.Suppl, pp.10-30, 2011.
DOI : 10.1038/sj.jid.5700739

E. Bouzigon, E. Corda, H. Aschard, M. Dizier, A. Boland et al., Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma, New England Journal of Medicine, vol.359, issue.19, pp.1985-94, 2008.
DOI : 10.1056/NEJMoa0806604
URL : https://hal.archives-ouvertes.fr/inserm-00335307

L. Smit, D. Strachan, R. Vermeulen, P. De-bakker, F. Demenais et al., Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?, European Respiratory Journal, vol.44, issue.5, pp.1234-1276, 2014.
DOI : 10.1183/09031936.00068014

C. Laprise and E. Bouzigon, To define the biological nature of asthma, Current Opinion in Allergy and Clinical Immunology, vol.11, issue.5, pp.391-393, 2011.
DOI : 10.1097/ACI.0b013e32834ae37e

P. Bégin and K. Nadeau, Epigenetic regulation of asthma and allergic disease, Allergy, Asthma & Clinical Immunology, vol.10, issue.1, p.27, 2014.
DOI : 10.1038/sj.ejcn.1602048

H. Harb and H. Renz, Update on epigenetics in allergic disease, Journal of Allergy and Clinical Immunology, vol.135, issue.1, pp.15-24, 2015.
DOI : 10.1016/j.jaci.2014.11.009

J. Bousquet, J. Farrell, G. Crooks, P. Hellings, E. Bel et al., Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5), Clinical and Translational Allergy, vol.2, issue.10, p.29, 2016.
DOI : 10.1016/S2213-2600(14)70188-2
URL : https://hal.archives-ouvertes.fr/hal-01821925

R. Bowman, C. Wright, M. Davidson, S. Francis, I. Yang et al., Epigenomic targets for the treatment of respiratory disease, Expert Opinion on Therapeutic Targets, vol.49, issue.6, pp.625-665, 2009.
DOI : 10.1146/annurev-pharmtox-061008-103102

S. Kangaspeska, B. Stride, R. Métivier, M. Polycarpou-schwarz, D. Ibberson et al., Transient cyclical methylation of promoter DNA, Nature, vol.21, issue.7183, pp.112-117, 2008.
DOI : 10.1038/nature06640
URL : https://hal.archives-ouvertes.fr/hal-00266286

J. Bousquet, K. J. Bateman, E. Viegi, G. Cruz, A. Khaltaev et al., Prioritised research agenda for prevention and control of chronic respiratory diseases, European Respiratory Journal, vol.36, issue.5, pp.995-1001, 2010.
DOI : 10.1183/09031936.00012610

M. Vernon, I. Wiklund, J. Bell, P. Dale, and K. Chapman, What Do We Know about Asthma Triggers? A Review of the Literature, Journal of Asthma, vol.18, issue.10, pp.991-999, 2012.
DOI : 10.1136/oem.2005.025916

H. Smits, P. Hiemstra, P. Da-costa, C. Ege, M. Edwards et al., Microbes and asthma: Opportunities for intervention, Journal of Allergy and Clinical Immunology, vol.137, issue.3, pp.690-697, 2016.
DOI : 10.1016/j.jaci.2016.01.004

R. Varraso and C. Camargo, Diet and asthma: need to account for asthma type and level of prevention, Expert Review of Respiratory Medicine, vol.10, issue.11, pp.1-4
DOI : 10.1183/13993003.00591-2015
URL : http://www.tandfonline.com/doi/pdf/10.1080/17476348.2016.1240033?needAccess=true

Y. Huang and H. Boushey, The microbiome in asthma, Journal of Allergy and Clinical Immunology, vol.135, issue.1, pp.25-30, 2015.
DOI : 10.1016/j.jaci.2014.11.011

S. Holgate and R. Polosa, Treatment strategies for allergy and asthma, Nature Reviews Immunology, vol.36, issue.3, pp.218-248, 2008.
DOI : 10.2174/187152807780077246

R. Raffa, S. Rawls, and E. Portyansky, Netter's Illustrated Pharmacology, 2014.

M. Gauthier, A. Ray, and S. Wenzel, Evolving Concepts of Asthma, American Journal of Respiratory and Critical Care Medicine, vol.154, issue.6, pp.660-668, 2015.
DOI : 10.1183/09031936.00073312
URL : http://europepmc.org/articles/pmc5447293?pdf=render

, Merriam-Webter's Collegiate Dictionary. 11th Edition: Springfield MM-WI, 2008.

M. Kabesch, Early origins of asthma (and allergy), Molecular and Cellular Pediatrics, vol.12, issue.9, p.31, 2016.
DOI : 10.1038/nrd4091

S. Wenzel, Asthma phenotypes: the evolution from clinical to molecular approaches, Nature Medicine, vol.123, issue.5, pp.716-741, 2012.
DOI : 10.1016/j.jaci.2009.01.057

L. Heaney and D. Robinson, Severe asthma treatment: need for characterising patients, The Lancet, vol.365, issue.9463, pp.974-980, 2005.
DOI : 10.1016/S0140-6736(05)71087-4
URL : https://pure.qub.ac.uk/portal/files/3690688/Lancet_2005_1_s2.0_S0140673605710874_main.pdf

J. Fingleton, J. Travers, M. Williams, T. Charles, D. Bowles et al., Treatment responsiveness of phenotypes of symptomatic airways obstruction in adults, Journal of Allergy and Clinical Immunology, vol.136, issue.3, pp.601-610, 2015.
DOI : 10.1016/j.jaci.2015.01.013

G. Skloot, P. Busse, S. Braman, E. Kovacs, A. Dixon et al., An Official American Thoracic Society Workshop Report: Evaluation and Management of Asthma in the Elderly, Annals of the American Thoracic Society, vol.105, issue.11, pp.2064-77, 2016.
DOI : 10.1097/SMJ.0b013e31825fed90

P. Gibson, V. Mcdonald, and G. Marks, Asthma in older adults, The Lancet, vol.376, issue.9743, pp.803-816, 2010.
DOI : 10.1016/S0140-6736(10)61087-2

N. Hanania, M. King, S. Braman, C. Saltoun, R. Wise et al., Asthma in the elderly: Current understanding and future research needs???a report of a National Institute on Aging (NIA) workshop, Journal of Allergy and Clinical Immunology, vol.128, issue.3, pp.4-24, 2011.
DOI : 10.1016/j.jaci.2011.06.048

A. Centre and A. Monitoring, Asthma in Australia AIHW Asthma Series no. 3. Cat. no. ACM 14. Canberra: AIHW, 2008.

T. Hartert, T. Speroff, A. Togias, E. Mitchel, M. Snowden et al., Risk factors for recurrent asthma hospital visits and death among a population of indigent older adults with asthma, Annals of Allergy, Asthma & Immunology, vol.89, issue.5, pp.467-73, 2002.
DOI : 10.1016/S1081-1206(10)62083-2

A. Banerji, S. Clark, M. Afilalo, M. Blanda, R. Cydulka et al., Prospective Multicenter Study of Acute Asthma in Younger Versus Older Adults Presenting to the Emergency Department, Journal of the American Geriatrics Society, vol.19, issue.(S, pp.48-55, 2006.
DOI : 10.1164/ajrccm.158.1.9707107

V. Plaza, J. Serra-batlles, M. Ferrer, and E. Morejón, Quality of Life and Economic Features in Elderly Asthmatics, Respiration, vol.67, issue.1, pp.65-70, 2000.
DOI : 10.1159/000029465

C. Reed, Asthma in the elderly: Diagnosis and management, Journal of Allergy and Clinical Immunology, vol.126, issue.4, pp.681-688, 2010.
DOI : 10.1016/j.jaci.2010.05.035

A. Yáñez, S. Cho, J. Soriano, L. Rosenwasser, G. Rodrigo et al., Asthma in the elderly: what we know and what we have yet to know, World Allergy Organ J, vol.7, issue.1, p.8, 2014.

P. Enright, R. Mcclelland, A. Newman, D. Gottlieb, and M. Lebowitz, Underdiagnosis and Undertreatment of Asthma in the Elderly, Chest, vol.116, issue.3, pp.603-616, 1999.
DOI : 10.1378/chest.116.3.603

S. Battaglia, A. Benfante, M. Spatafora, and N. Scichilone, Asthma in the elderly: a different disease? Breathe (Sheff), pp.18-28, 2016.

J. Travers, S. Marsh, M. Williams, M. Weatherall, B. Caldwell et al., External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?, Thorax, vol.62, issue.3, pp.219-242, 2007.
DOI : 10.1136/thx.2006.066837

M. Salive, Multimorbidity in Older Adults, Epidemiologic Reviews, vol.25, issue.5, pp.75-83, 2013.
DOI : 10.1007/s11606-009-1232-1

C. Bähler, C. Huber, B. Brüngger, and O. Reich, Multimorbidity, health care utilization and costs in an elderly community-dwelling population: a claims data based observational study, BMC Health Services Research, vol.107, issue.2???3, p.23, 2015.
DOI : 10.1016/j.healthpol.2012.06.006

S. Mercer, Comorbidity in asthma is important and requires a generalist approach, Primary Care Respiratory Journal, vol.23, issue.1, pp.4-5, 2014.
DOI : 10.1136/bmj.e5205

A. Gershon, C. Wang, J. Guan, and T. To, Burden of comorbidity in individuals with asthma, Thorax, vol.65, issue.7, pp.612-620, 2010.
DOI : 10.1136/thx.2009.131078

L. Boulet, Influence of comorbid conditions on asthma, European Respiratory Journal, vol.33, issue.4, pp.897-906, 2009.
DOI : 10.1183/09031936.00121308

M. Cazzola, A. Segreti, L. Calzetta, and P. Rogliani, Comorbidities of asthma, Current Opinion in Pulmonary Medicine, vol.19, issue.1, pp.36-41, 2013.
DOI : 10.1097/MCP.0b013e32835b113a

W. Song and S. Cho, Challenges in the Management of Asthma in the Elderly, Allergy, Asthma & Immunology Research, vol.7, issue.5, pp.431-440, 2015.
DOI : 10.4168/aair.2015.7.5.431

L. Boulet and M. Boulay, Asthma-related comorbidities, Expert Review of Respiratory Medicine, vol.29, issue.3, pp.377-93, 2011.
DOI : 10.1016/0022-3999(85)90042-X

R. Adams, D. Wilson, A. Taylor, A. Daly, E. Tursan-d-'espaignet et al., Coexistent Chronic Conditions and Asthma Quality of Life, Chest, vol.129, issue.2, pp.285-91, 2006.
DOI : 10.1378/chest.129.2.285

W. Chen, L. Lynd, J. Fitzgerald, C. Marra, R. Balshaw et al., Excess medical costs in patients with asthma and the role of comorbidity, European Respiratory Journal, vol.48, issue.6, 2016.
DOI : 10.1183/13993003.01141-2016

, Global Initiative for Chronic Lung Obstructive Disease. Global Strategy for the Diagnosis, Management and Prevention of COPD 2017. www.goldcopd.org. Date last updated: 2016. Date last accessed, 2016.

H. Kankaanranta, P. Kauppi, L. Tuomisto, and P. Ilmarinen, Emerging Comorbidities in Adult Asthma: Risks, Clinical Associations, and Mechanisms, Mediators of Inflammation, vol.74, issue.3, p.3690628, 2016.
DOI : 10.1016/j.pharmthera.2005.10.015

A. Wardzy?ska, B. Kubsik, and M. Kowalski, Comorbidities in elderly patients with asthma: Association with control of the disease and concomitant treatment, Geriatrics & Gerontology International, vol.32, issue.13, pp.902-911, 2015.
DOI : 10.1016/j.amjoto.2009.11.002

G. Rodrigo and J. Castro-rodríguez, What Is the Role of Tiotropium in Asthma?, Chest, vol.147, issue.2, pp.388-96, 2015.
DOI : 10.1378/chest.14-1698

K. Chung, S. Wenzel, J. Brozek, A. Bush, M. Castro et al., International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma, European Respiratory Journal, vol.43, issue.2, pp.343-73, 2014.
DOI : 10.1183/09031936.00202013

A. Dima, G. Hernandez, O. Cunillera, M. Ferrer, M. De-bruin et al., Asthma inhaler adherence determinants in adults: systematic review of observational data, European Respiratory Journal, vol.45, issue.4, pp.994-1018, 2015.
DOI : 10.1183/09031936.00172114

A. Dixon, Long-acting ??-Agonists and Asthma: The Saga Continues, American Journal of Respiratory and Critical Care Medicine, vol.184, issue.11, pp.1220-1221, 2011.
DOI : 10.1164/ajrccm.158.3.9801035

W. Castle, R. Fuller, J. Hall, and J. Palmer, Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment., BMJ, vol.306, issue.6884
DOI : 10.1136/bmj.306.6884.1034

, BMJ, vol.306, issue.6884, pp.1034-1041, 1993.

K. Basu, C. Palmer, R. Tavendale, B. Lipworth, and S. Mukhopadhyay, Adrenergic ??2-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol, Journal of Allergy and Clinical Immunology, vol.124, issue.6, pp.1188-94, 2009.
DOI : 10.1016/j.jaci.2009.07.043

B. Chowdhury and G. Dal-pan, The FDA and Safe Use of Long-Acting Beta-Agonists in the Treatment of Asthma, New England Journal of Medicine, vol.362, issue.13, pp.1169-71, 2010.
DOI : 10.1056/NEJMp1002074

C. Camargo, K. Davis, E. Andrews, D. Stempel, and M. Schatz, Pharmacoepidemiological Study of Long-Acting ??-agonist/Inhaled Corticosteroid Therapy and Asthma Mortality: Clinical Implications, Clinical Drug Investigation, vol.100, issue.6, pp.993-1002, 2016.
DOI : 10.1016/S1081-1206(10)60048-8

N. Gross and P. Barnes, New Therapies for Asthma and COPD, Am J Respir Crit Care Med, 2016.

K. Tantisira, A. Damask, S. Szefler, B. Schuemann, A. Markezich et al., Gene as a Novel Asthma Pharmacogenetic Locus, American Journal of Respiratory and Critical Care Medicine, vol.115, issue.12, pp.1286-91, 2012.
DOI : 10.1056/NEJMoa0911353

K. Tantisira, J. Lasky-su, M. Harada, A. Murphy, A. Litonjua et al., and Response to Glucocorticoid Therapy in Asthma, New England Journal of Medicine, vol.365, issue.13, pp.1173-83, 2011.
DOI : 10.1056/NEJMoa0911353

H. Park, A. Dahlin, S. Tse, Q. Duan, B. Schuemann et al., Genetic predictors associated with improvement of asthma symptoms in response to inhaled corticosteroids, Journal of Allergy and Clinical Immunology, vol.133, issue.3, pp.664-673, 2014.
DOI : 10.1016/j.jaci.2013.12.1042

V. Ortega, Pharmacogenetics of beta2 adrenergic receptor agonists in asthma management, Clinical Genetics, vol.13, issue.1
DOI : 10.1097/ACI.0b013e3283630c19

, Clin Genet, vol.86, issue.1, pp.12-20, 2014.

J. Lima, Do genetic polymorphisms alter patient response to inhaled bronchodilators?, Expert Opinion on Drug Metabolism & Toxicology, vol.11, issue.9, pp.1231-1271, 2014.
DOI : 10.1097/FPC.0b013e32833428d0

V. Ortega, D. Meyers, and E. Bleecker, Asthma pharmacogenetics and the development of genetic profiles for personalized medicine, Pharmgenomics Pers Med, vol.8, pp.9-22, 2015.

J. Bice, E. Leechawengwongs, and A. Montanaro, Biologic targeted therapy in allergic asthma, Annals of Allergy, Asthma & Immunology, vol.112, issue.2, pp.108-123, 2014.
DOI : 10.1016/j.anai.2013.12.013

E. De-roos, J. In-'t-veen, G. Braunstahl, L. Lahousse, and G. Brusselle, Targeted Therapy for Older Patients with Uncontrolled Severe Asthma: Current and Future Prospects, Drugs & Aging, vol.42, issue.5, pp.619-647, 2016.
DOI : 10.1183/09031936.00093913

O. Golubnitschaja, V. Costigliola, and E. , General Report & Recommendations in Predictive, Preventive and Personalised Medicine 2012: White Paper of the European Association for Predictive, Preventive and Personalised Medicine, EPMA Journal, vol.3, issue.1, p.14, 2012.
DOI : 10.1186/1878-5085-3-14

S. Suissa and P. Ernst, Inhaled corticosteroids: Impact on asthma morbidity and mortality, Journal of Allergy and Clinical Immunology, vol.107, issue.6, pp.937-981, 2001.
DOI : 10.1067/mai.2001.115653

B. Bereznicki, G. Peterson, S. Jackson, E. Walters, K. Fitzmaurice et al., Data-mining of medication records to improve asthma management, Med J Aust, vol.189, issue.1, pp.21-26, 2008.

Y. Takahashi, Y. Nishida, and S. Asai, Utilization of health care databases for pharmacoepidemiology, European Journal of Clinical Pharmacology, vol.82, issue.2, pp.123-132, 2012.
DOI : 10.1038/sj.clpt.6100249

A. Dijkstra, J. Vonk, H. Jongepier, G. Koppelman, J. Schouten et al., Lung function decline in asthma: association with inhaled corticosteroids, smoking and sex, Thorax, vol.61, issue.2, pp.105-115, 2006.
DOI : 10.1136/thx.2004.039271
URL : http://thorax.bmj.com/content/thoraxjnl/61/2/105.full.pdf

P. Lange, H. Scharling, C. Ulrik, and J. Vestbo, Inhaled corticosteroids and decline of lung function in community residents with asthma, Thorax, vol.61, issue.2, pp.100-104, 2006.
DOI : 10.1136/thx.2004.037978
URL : http://thorax.bmj.com/content/thoraxjnl/61/2/100.full.pdf

R. De-marco, A. Marcon, D. Jarvis, S. Accordini, M. Bugiani et al., Inhaled steroids are associated with reduced lung function decline in subjects with asthma with elevated total IgE, Journal of Allergy and Clinical Immunology, vol.119, issue.3, pp.611-618, 2007.
DOI : 10.1016/j.jaci.2006.11.696
URL : https://hal.archives-ouvertes.fr/inserm-00347226

T. Shimoda, Y. Obase, R. Kishikawa, and T. Iwanaga, Impact of Inhaled Corticosteroid Treatment on 15-Year Longitudinal Respiratory Function Changes in Adult Patients with Bronchial Asthma, International Archives of Allergy and Immunology, vol.162, issue.4, pp.323-332, 2013.
DOI : 10.1159/000353910

W. Ray, Evaluating Medication Effects Outside of Clinical Trials: New-User Designs, American Journal of Epidemiology, vol.158, issue.9, pp.915-935, 2003.
DOI : 10.1093/aje/kwg231
URL : https://academic.oup.com/aje/article-pdf/158/9/915/238723/kwg231.pdf

G. Danaei, M. Tavakkoli, and M. Hernán, Bias in Observational Studies of Prevalent Users: Lessons for Comparative Effectiveness Research From a Meta-Analysis of Statins, American Journal of Epidemiology, vol.36, issue.6, pp.250-62, 2012.
DOI : 10.1016/S0735-1097(00)00950-5

M. Fischer, M. Stedman, J. Lii, C. Vogeli, W. Shrank et al., Primary Medication Non-Adherence: Analysis of 195,930 Electronic Prescriptions, Journal of General Internal Medicine, vol.21, issue.8, pp.284-90, 2010.
DOI : 10.1093/jnci/94.9.652
URL : http://europepmc.org/articles/pmc2842539?pdf=render

O. Klungel, A. De-boer, A. Paes, R. Herings, J. Seidell et al., Influence of question structure on the recall of self-reported drug use, Journal of Clinical Epidemiology, vol.53, issue.3, pp.273-280, 2000.
DOI : 10.1016/S0895-4356(99)00167-5

H. Lau, A. De-boer, K. Beuning, and A. Porsius, Validation of pharmacy records in drug exposure assessment, Journal of Clinical Epidemiology, vol.50, issue.5, pp.619-644, 1997.
DOI : 10.1016/S0895-4356(97)00040-1

A. Bowling, Mode of questionnaire administration can have serious effects on data quality, Journal of Public Health, vol.27, issue.3, pp.281-91, 2005.
DOI : 10.1093/ije/27.6.935
URL : https://academic.oup.com/jpubhealth/article-pdf/27/3/281/4347729/fdi031.pdf

H. Gama, S. Correia, and N. Lunet, Questionnaire design and the recall of pharmacological treatments: a systematic review, Pharmacoepidemiology and Drug Safety, vol.164, issue.12, pp.175-87, 2009.
DOI : 10.1111/j.1532-5415.1991.tb02872.x

S. Silverman, From Randomized Controlled Trials to Observational Studies, The American Journal of Medicine, vol.122, issue.2, pp.114-134, 2009.
DOI : 10.1016/j.amjmed.2008.09.030

B. Wettermark, H. Zoëga, K. Furu, M. Korhonen, J. Hallas et al., The Nordic prescription databases as a resource for pharmacoepidemiological research-a literature review, Pharmacoepidemiology and Drug Safety, vol.112, issue.Suppl 1, pp.691-700, 2013.
DOI : 10.1111/j.1742-7843.2012.00928.x

M. Schatz, R. Nakahiro, W. Crawford, G. Mendoza, D. Mosen et al., Asthma Quality-of-Care Markers Using Administrative Data, Chest, vol.128, issue.4, pp.1968-73, 2005.
DOI : 10.1378/chest.128.4.1968

M. Schatz, R. Zeiger, W. Vollmer, D. Mosen, G. Mendoza et al., The Controller-to-Total Asthma Medication Ratio Is Associated With Patient-Centered As Well As Utilization Outcomes, Chest, vol.130, issue.1, pp.43-50, 2006.
DOI : 10.1378/chest.130.1.43

M. Schatz and D. Stempel, Asthma quality-of-care measures using administrative data: relationships to subsequent exacerbations in multiple databases, Annals of Allergy, Asthma & Immunology, vol.101, issue.3, pp.235-244, 2008.
DOI : 10.1016/S1081-1206(10)60487-5

M. Broder, B. Gutierrez, E. Chang, D. Meddis, and M. Schatz, Ratio of controller to total asthma medications: determinants of the measure, Am J Manag Care, vol.16, issue.3, pp.170-178, 2010.

A. Andrews, A. Simpson, W. Basco, and R. Teufel, Asthma Medication Ratio Predicts Emergency Department Visits and Hospitalizations in Children with Asthma, Medicare & Medicaid Research Review, vol.3, issue.4, 2013.
DOI : 10.5600/mmrr.003.04.a05
URL : https://doi.org/10.5600/mmrr.003.04.a05

L. Laforest, I. Licaj, G. Devouassoux, G. Chatte, J. Martin et al., Asthma drug ratios and exacerbations: claims data from universal health coverage systems, European Respiratory Journal, vol.43, issue.5, pp.1378-86, 2014.
DOI : 10.1183/09031936.00100113
URL : https://hal.archives-ouvertes.fr/hal-01838982

B. Strom, S. Kimmel, S. Hennessy, and . Pharmaoepidemiology, , 2005.

M. Winglee, R. Valliant, and F. Scheuren, A case study in record linkage, Statistics Canada, vol.31, issue.1, pp.3-11, 2005.

L. Braitman and P. Rosenbaum, Rare Outcomes, Common Treatments: Analytic Strategies Using Propensity Scores, Annals of Internal Medicine, vol.137, issue.8, pp.693-698, 2002.
DOI : 10.7326/0003-4819-137-8-200210150-00015
URL : http://www-stat.wharton.upenn.edu/~rosenbap/AIMeditorial.pdf

P. Arbogast and W. Ray, Performance of Disease Risk Scores, Propensity Scores, and Traditional Multivariable Outcome Regression in the Presence of Multiple Confounders, American Journal of Epidemiology, vol.163, issue.12, pp.613-633, 2011.
DOI : 10.1093/aje/kwj149

O. Dumas, V. Siroux, L. Moual, N. Varraso, and R. ,

, Rev Epidemiol Sante Publique, vol.62, issue.1, pp.53-63, 2014.

J. Labarère, J. Bosson, P. François, and M. Fine, L???analyse par score de propension, La Revue de M??decine Interne, vol.29, issue.3, pp.255-263, 2008.
DOI : 10.1016/j.revmed.2007.08.001

S. Schneeweiss, Developments in Post-marketing Comparative Effectiveness Research, Clinical Pharmacology & Therapeutics, vol.52, issue.2, pp.143-56, 2007.
DOI : 10.7326/0003-4819-141-2-200407200-00008
URL : http://europepmc.org/articles/pmc2905665?pdf=render

D. Agostino, R. , and J. , Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group, Statistics in Medicine, vol.17, issue.19, pp.2265-81, 1998.
DOI : 10.1002/(SICI)1097-0258(19981015)17:19<2265::AID-SIM918>3.0.CO;2-B

G. Heinze and P. Jüni, An overview of the objectives of and the approaches to propensity score analyses, European Heart Journal, vol.56, issue.14, pp.1704-1712, 2011.
DOI : 10.1111/j.0006-341X.2000.00249.x

M. Brookhart, S. Schneeweiss, K. Rothman, R. Glynn, J. Avorn et al., Variable Selection for Propensity Score Models, American Journal of Epidemiology, vol.163, issue.12, pp.1149-56, 2006.
DOI : 10.1016/j.csda.2004.08.013
URL : https://academic.oup.com/aje/article-pdf/163/12/1149/223159/kwj149.pdf

S. Weitzen, K. Lapane, A. Toledano, A. Hume, and V. Mor, Principles for modeling propensity scores in medical research: a systematic literature review, Pharmacoepidemiology and Drug Safety, vol.286, issue.12, pp.841-53, 2004.
DOI : 10.1001/jama.286.16.1977

R. Glynn, S. Schneeweiss, and T. Stürmer, Indications for Propensity Scores and Review of their Use in Pharmacoepidemiology, Basic <html_ent glyph="@amp;" ascii="&"/> Clinical Pharmacology <html_ent glyph="@amp;" ascii="&"/> Toxicology, vol.127, issue.3, pp.253-262, 2006.
DOI : 10.1002/pds.986

A. Karahalios, L. Baglietto, J. Carlin, D. English, and J. Simpson, A review of the reporting and handling of missing data in cohort studies with repeated assessment of exposure measures, BMC Medical Research Methodology, vol.168, issue.177
DOI : 10.1001/archinte.168.6.643

, BMC Med Res Methodol, vol.12, p.96, 2012.

M. Powney, P. Williamson, J. Kirkham, and R. Kolamunnage-dona, A review of the handling of missing longitudinal outcome data in clinical trials, Trials, vol.15, issue.1, p.237, 2014.
DOI : 10.1016/S2213-2600(13)70037-7

D. Rubin, Inference and missing data, Biometrika, vol.63, issue.3, pp.581-592, 1976.
DOI : 10.1093/biomet/63.3.581

J. Schafer and J. Graham, Missing data: Our view of the state of the art., Psychological Methods, vol.7, issue.2, pp.147-77, 2002.
DOI : 10.1037/1082-989X.7.2.147

P. Hayati-rezvan, K. Lee, and J. Simpson, The rise of multiple imputation: a review of the reporting and implementation of the method in medical research, BMC Medical Research Methodology, vol.13, issue.1, p.30, 2015.
DOI : 10.1186/1471-2288-13-144

Y. Xiao, R. Song, M. Chen, and H. Hall, Direct and unbiased multiple imputation methods for missing values of categorical variables, J Data Sci, vol.10, pp.465-81, 2012.

J. Graham, A. Olchowski, and T. Gilreath, How Many Imputations are Really Needed? Some Practical Clarifications of Multiple Imputation Theory, Prevention Science, vol.33, issue.3, pp.206-219, 2007.
DOI : 10.1201/9781439821862

F. Kauffmann, M. Dizier, I. Pin, E. Paty, F. Gormand et al., Epidemiological Study of the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy, American Journal of Respiratory and Critical Care Medicine, vol.127, issue.4, pp.123-132, 1997.
DOI : 10.1164/ajrccm/146.3.633
URL : https://hal.archives-ouvertes.fr/hal-00596474

F. Kauffmann, M. Dizier, I. Annesi-maesano, J. Bousquet, D. Charpin et al., EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy)--descriptive characteristics, Clin Exp Allergy, vol.29, issue.4, pp.17-21, 1999.
URL : https://hal.archives-ouvertes.fr/hal-00596450

F. Clavel-chapelon, M. Van-liere, C. Giubout, M. Niravong, H. Goulard et al.,

, Etude Epidémiologique auprès de femmes de l'Education Nationale, E3N, a French cohort study on cancer risk factors. E3N Group, pp.473-481, 1997.

O. Klungel, E. Martens, B. Psaty, D. Grobbee, S. Sullivan et al., Methods to assess intended effects of drug treatment in observational studies are reviewed, Journal of Clinical Epidemiology, vol.57, issue.12, pp.1223-1254, 2004.
DOI : 10.1016/j.jclinepi.2004.03.011

G. Fang, J. Brooks, and E. Chrischilles, Comparison of Instrumental Variable Analysis Using a New Instrument With Risk Adjustment Methods to Reduce Confounding by Indication, American Journal of Epidemiology, vol.62, issue.2, pp.1142-51, 2012.
DOI : 10.2307/2951620

I. Adcock and K. Ito, Steroid resistance in asthma: a major problem requiring novel solutions or a non-issue?, Current Opinion in Pharmacology, vol.4, issue.3, pp.257-62, 2004.
DOI : 10.1016/j.coph.2004.02.001

, Global Initiative for Asthma Global strategy for asthma management and prevention. Update 2012. www.ginasthma.org. Date last updated: 2012. Date last accessed, 2013.

S. Suissa, P. Ernst, and A. Kezouh, Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma, Thorax, vol.57, issue.10, pp.880-884, 2002.
DOI : 10.1136/thorax.57.10.880

R. Franco, A. Santos, H. Nascimento, C. Souza-machado, E. Ponte et al., Cost-effectiveness analysis of a state funded programme for control of severe asthma, BMC Public Health, vol.32, issue.1, p.82, 2007.
DOI : 10.1016/0021-9681(79)90012-2

T. Zhang, M. Smith, P. Camp, and B. Carleton, High use of health services in patients with suboptimal asthma drug regimens: a population-based assessment in British Columbia, Canada, Pharmacoepidemiology and Drug Safety, vol.45, issue.7, pp.744-51, 2013.
DOI : 10.1080/02770900801911178

V. Siroux, A. Boudier, J. Bousquet, J. Bresson, J. Cracowski et al., Phenotypic determinants of uncontrolled asthma, Journal of Allergy and Clinical Immunology, vol.124, issue.4, pp.681-688, 2009.
DOI : 10.1016/j.jaci.2009.06.010
URL : https://hal.archives-ouvertes.fr/inserm-00422525

S. Standardization, Update Am J Respir Crit Care Med, vol.152, issue.3, pp.1107-1143, 1994.

S. Stanojevic, A. Wade, J. Stocks, J. Hankinson, A. Coates et al., Reference Ranges for Spirometry Across All Ages, American Journal of Respiratory and Critical Care Medicine, vol.177, issue.3, pp.253-60, 2008.
DOI : 10.1186/1465-9921-8-14

E. Juniper, G. Guyatt, P. Ferrie, and L. Griffith, Measuring Quality of Life in Asthma, American Review of Respiratory Disease, vol.126, issue.4, pp.832-840, 1993.
DOI : 10.1378/chest.90.4.575

E. Juniper, G. Guyatt, A. Willan, and L. Griffith, Determining a minimal important change in a disease-specific quality of life questionnaire, Journal of Clinical Epidemiology, vol.47, issue.1, pp.81-88, 1994.
DOI : 10.1016/0895-4356(94)90036-1

E. Bouzigon, V. Siroux, M. Dizier, A. Lemainque, C. Pison et al., Scores of asthma and asthma severity reveal new regions of linkage in EGEA study families, European Respiratory Journal, vol.30, issue.2, pp.253-262, 2007.
DOI : 10.1183/09031936.00162206

A. Mattei and . Mf, Estimating and using propensity score in presence of missing background data: an application to assess the impact of childbearing on wellbeing, Statistical Methods and Applications, vol.18, issue.1, pp.257-73, 2009.
DOI : 10.1007/s10260-007-0086-0

L. Osterberg and T. Blaschke, Adherence to Medication, New England Journal of Medicine, vol.353, issue.5, pp.487-97, 2005.
DOI : 10.1056/NEJMra050100

M. Cochrane, M. Bala, K. Downs, J. Mauskopf, B. et al., Inhaled Corticosteroids for Asthma Therapy, Chest, vol.117, issue.2, pp.542-50, 2000.
DOI : 10.1378/chest.117.2.542

R. Wyss, C. Girman, R. Locasale, A. Brookhart, and T. Sturmer, Variable selection for propensity score models when estimating treatment effects on multiple outcomes: a simulation study, Pharmacoepidemiology and Drug Safety, vol.12, issue.3, pp.77-85, 2013.
DOI : 10.1097/00001648-200105000-00011
URL : http://europepmc.org/articles/pmc3540180?pdf=render

P. Austin, P. Grootendorst, and G. Anderson, A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study, Statistics in Medicine, vol.2, issue.4, pp.734-53, 2007.
DOI : 10.1007/978-1-4757-2443-1

P. Austin, The Relative Ability of Different Propensity Score Methods to Balance Measured Covariates Between Treated and Untreated Subjects in Observational Studies, Medical Decision Making, vol.39, issue.6, pp.661-77, 2009.
DOI : 10.1002/sim.2053

G. Biondi-zoccai, E. Romagnoli, P. Agostoni, D. Capodanno, D. Castagno et al., Are propensity scores really superior to standard multivariable analysis?, Contemporary Clinical Trials, vol.32, issue.5, pp.731-771, 2011.
DOI : 10.1016/j.cct.2011.05.006

B. Shah, A. Laupacis, J. Hux, and P. Austin, Propensity score methods gave similar results to traditional regression modeling in observational studies: a systematic review, Journal of Clinical Epidemiology, vol.58, issue.6, pp.550-559, 2005.
DOI : 10.1016/j.jclinepi.2004.10.016

T. Sturmer, M. Joshi, R. Glynn, J. Avorn, K. Rothman et al., A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods, Journal of Clinical Epidemiology, vol.59, issue.5, pp.437-484, 2006.
DOI : 10.1016/j.jclinepi.2005.07.004

, http://apps.who.int. Date last update: 2015. Date last accessed, World Health Organization. World Report on Ageing and Health, 2016.

M. Sanchez, J. Bousquet, L. Moual, N. Jacquemin, B. Clavel-chapelon et al., Temporal Asthma Patterns Using Repeated Questionnaires over 13 Years in a Large French Cohort of Women, PLoS ONE, vol.43, issue.5, p.65090, 2013.
DOI : 10.1371/journal.pone.0065090.s001
URL : https://hal.archives-ouvertes.fr/inserm-01325058

. Who-collaborating-centre-for-drug-statistics and . Methodology, Guidelines for ATC classification and DDD assignement 2016, 2016.

O. Savenije, R. Granell, D. Caudri, G. Koppelman, H. Smit et al., Comparison of childhood wheezing phenotypes in 2 birth cohorts: ALSPAC and PIAMA, Journal of Allergy and Clinical Immunology, vol.127, issue.6, pp.1505-1517, 2011.
DOI : 10.1016/j.jaci.2011.02.002

A. Custovic, H. Sonntag, I. Buchan, D. Belgrave, A. Simpson et al., Evolution pathways of IgE responses to grass and mite allergens throughout childhood, Journal of Allergy and Clinical Immunology, vol.136, issue.6, pp.1645-52, 2015.
DOI : 10.1016/j.jaci.2015.03.041

H. Reddel, D. Taylor, E. Bateman, L. Boulet, H. Boushey et al., An Official American Thoracic Society/European Respiratory Society Statement: Asthma Control and Exacerbations, American Journal of Respiratory and Critical Care Medicine, vol.180, issue.1, pp.59-99, 2009.
DOI : 10.1046/j.1472-9725.2001.00007.x

R. Barr, J. Herbstman, F. Speizer, and C. Camargo, Validation of Self-reported Chronic Obstructive Pulmonary Disease in a Cohort Study of Nurses, American Journal of Epidemiology, vol.155, issue.10, pp.965-71, 2002.
DOI : 10.1093/aje/155.10.965

A. Melani, Management of asthma in the elderly patient, Clinical Interventions in Aging, vol.8, pp.913-935, 2013.
DOI : 10.2147/CIA.S33609

M. Schatz, R. Zeiger, S. Yang, W. Chen, W. Crawford et al., Relationship of asthma control to asthma exacerbations using surrogate markers within a managed care database, Am J Manag Care, vol.16, issue.5, pp.327-360, 2010.

U. Frey, T. Brodbeck, A. Majumdar, D. Taylor, G. Town et al., Risk of severe asthma episodes predicted from fluctuation analysis of airway function, Nature, vol.92, issue.suppl., pp.667-70, 2005.
DOI : 10.1152/japplphysiol.00675.2001

U. Frey and S. B. , Complexity of chronic asthma and chronic obstructive pulmonary disease: implications for risk assessment, and disease progression and control, The Lancet, vol.372, issue.9643, pp.1088-99, 2008.
DOI : 10.1016/S0140-6736(08)61450-6

C. Thamrin, J. Zindel, R. Nydegger, H. Reddel, P. Chanez et al., Predicting future risk of asthma exacerbations using individual conditional probabilities, Journal of Allergy and Clinical Immunology, vol.127, issue.6, pp.1494-502, 2011.
DOI : 10.1016/j.jaci.2011.01.018

H. Sbihi, M. Koehoorn, L. Tamburic, and M. Brauer, Asthma Trajectories in a Population-based Birth Cohort. Impacts of Air Pollution and Greenness, American Journal of Respiratory and Critical Care Medicine, vol.122, issue.5, 2016.
DOI : 10.1371/journal.pone.0048359

K. Nylund, T. Asparouhov, and B. Muthén, Deciding on the Number of Classes in Latent Class Analysis and Growth Mixture Modeling: A Monte Carlo Simulation Study, Structural Equation Modeling: A Multidisciplinary Journal, vol.9, issue.4, pp.535-69, 2007.
DOI : 10.2307/1912557

R. Faner, T. Cruz, A. López-giraldo, and A. Agustí, Network medicine, multimorbidity and the lung in the elderly, European Respiratory Journal, vol.44, issue.3, pp.775-88, 2014.
DOI : 10.1183/09031936.00078714

C. Hidalgo, N. Blumm, A. Barabási, and N. Christakis, A Dynamic Network Approach for the Study of Human Phenotypes, PLoS Computational Biology, vol.21, issue.4, p.1000353, 2009.
DOI : 10.1371/journal.pcbi.1000353.s001

J. Hu, C. Thomas, and S. Brunak, Network biology concepts in complex disease comorbidities, Nature Reviews Genetics, vol.219, issue.10, 2016.
DOI : 10.1093/bioinformatics/btr052

V. Siroux, A. Boudier, J. Bousquet, L. Vignoud, F. Gormand et al., Asthma control assessed in the EGEA epidemiological survey and health-related quality of??life, Respiratory Medicine, vol.106, issue.6, pp.820-828, 2012.
DOI : 10.1016/j.rmed.2012.01.009
URL : https://hal.archives-ouvertes.fr/inserm-00742663

M. Bastian, S. Heymann, and J. M. Gephi, An Open Source Software for Exploring and Manipulating Networks. www.gephi.org. Date last updated: 2009. Date last accessed, 2016.

M. Divo, C. Casanova, J. Marin, V. Pinto-plata, J. De-torres et al., COPD comorbidities network, European Respiratory Journal, vol.46, issue.3, pp.640-50, 2015.
DOI : 10.1183/09031936.00171614

A. Agusti, P. Sobradillo, and B. Celli, Addressing the Complexity of Chronic Obstructive Pulmonary Disease, American Journal of Respiratory and Critical Care Medicine, vol.183, issue.9, pp.1129-1166, 2011.
DOI : 10.1513/pats.200701-004FM

J. Van-boven, M. Román-rodríguez, and J. Palmer,

. Comorbidome, Pattern, and Impact of Asthma-COPD Overlap Syndrome in Real Life, Chest, vol.149, issue.4, pp.1011-1031, 2016.

R. Maher, J. Hanlon, and E. Hajjar, Clinical consequences of polypharmacy in elderly, Expert Opinion on Drug Safety, vol.5, issue.1, pp.57-65, 2014.
DOI : 10.2165/00003495-200969040-00001

D. Qato, G. Alexander, R. Conti, M. Johnson, P. Schumm et al., Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States, JAMA, vol.300, issue.24, pp.2867-78, 2008.

V. Siroux, J. González, E. Bouzigon, I. Curjuric, A. Boudier et al., Genetic heterogeneity of asthma phenotypes identified by a clustering approach, European Respiratory Journal, vol.43, issue.2, pp.439-52, 2014.
DOI : 10.1183/09031936.00032713

C. Iribarren, I. Tolstykh, and M. Eisner, Are patients with asthma at increased risk of coronary heart disease?, International Journal of Epidemiology, vol.33, issue.4, pp.743-751, 2004.
DOI : 10.1093/ije/dyh081

S. Onufrak, J. Abramson, H. Austin, F. Holguin, W. Mcclellan et al., Relation of Adult-Onset Asthma to Coronary Heart Disease and Stroke, The American Journal of Cardiology, vol.101, issue.9, pp.1247-52, 2008.
DOI : 10.1016/j.amjcard.2007.12.024

M. Murakami and T. Hirano, The molecular mechanisms of chronic inflammation development

, Front Immunol, vol.3, p.323, 2012.

B. Bolon, Cellular and Molecular Mechanisms of Autoimmune Disease, Toxicologic Pathology, vol.40, issue.569068, pp.216-245, 2012.
DOI : 10.1093/hmg/ddp432

M. Engelkes, H. Janssens, J. De-jongste, M. Sturkenboom, and K. Verhamme, Medication adherence and the risk of severe asthma exacerbations: a systematic review, European Respiratory Journal, vol.45, issue.2, pp.396-407, 2015.
DOI : 10.1183/09031936.00075614
URL : http://erj.ersjournals.com/content/erj/45/2/396.full.pdf

L. Williams, E. Peterson, K. Wells, B. Ahmedani, R. Kumar et al., Quantifying the proportion of severe asthma exacerbations attributable to inhaled corticosteroid nonadherence, Journal of Allergy and Clinical Immunology, vol.128, issue.6, pp.1185-91, 2011.
DOI : 10.1016/j.jaci.2011.09.011
URL : http://europepmc.org/articles/pmc3229671?pdf=render

L. Laforest, M. Belhassen, G. Devouassoux, A. Didier, M. Ginoux et al., Long-Term Inhaled Corticosteroid Adherence in Asthma Patients with Short-Term Adherence, The Journal of Allergy and Clinical Immunology: In Practice, vol.4, issue.5, pp.890-899, 2016.
DOI : 10.1016/j.jaip.2016.07.008
URL : https://hal.archives-ouvertes.fr/hal-01838972

D. Lee, J. Park, K. Kay, N. Christakis, Z. Oltvai et al., The implications of human metabolic network topology for disease comorbidity, Proceedings of the National Academy of Sciences, vol.104, issue.31, pp.9880-9885, 2008.
DOI : 10.1073/pnas.0609845104
URL : http://www.pnas.org/content/105/29/9880.full.pdf

T. Ideker and N. Krogan, Differential network biology, Molecular Systems Biology, vol.11, p.565, 2012.
DOI : 10.1038/msb.2009.80
URL : http://msb.embopress.org/content/msb/8/1/565.full.pdf

P. Peduzzi, J. Concato, E. Kemper, T. Holford, and A. Feinstein, A simulation study of the number of events per variable in logistic regression analysis, Journal of Clinical Epidemiology, vol.49, issue.12, pp.1373-1382, 1996.
DOI : 10.1016/S0895-4356(96)00236-3

M. Cepeda, R. Boston, J. Farrar, and B. Strom, Comparison of Logistic Regression versus Propensity Score When the Number of Events Is Low and There Are Multiple Confounders, American Journal of Epidemiology, vol.158, issue.3, pp.280-287, 2003.
DOI : 10.1093/aje/kwg115

B. Lee, J. Lessler, and E. Stuart, Improving propensity score weighting using machine learning, Statistics in Medicine, vol.2, issue.3??????4
DOI : 10.1111/j.1365-2656.2008.01390
URL : http://europepmc.org/articles/pmc2807890?pdf=render

, Stat Med, vol.29, issue.3, pp.337-383, 2010.

C. Hurault-delarue, C. Chouquet, N. Savy, I. Lacroix, A. Beau et al., How to take into account exposure to drugs over time in pharmacoepidemiology studies of pregnant women?, Pharmacoepidemiology and Drug Safety, vol.370, issue.194, pp.770-777, 2016.
DOI : 10.1056/NEJMoa1312828
URL : https://hal.archives-ouvertes.fr/hal-01864258

F. Feuillet, L. Bellanger, J. Hardouin, C. Victorri-vigneau, and V. Sébille, On Comparison of Clustering Methods for Pharmacoepidemiological Data, Journal of Biopharmaceutical Statistics, vol.27, issue.4, pp.843-56, 2015.
DOI : 10.1080/01621459.1963.10500845
URL : https://hal.archives-ouvertes.fr/hal-00997772

S. Yu, H. Chang, M. Lin, and Y. Lin, Agreement between self-reported and health insurance claims on utilization of health care: A population study, Journal of Clinical Epidemiology, vol.62, issue.12, pp.1316-1338, 2009.
DOI : 10.1016/j.jclinepi.2009.01.016

J. Bousquet, J. Michel, T. Standberg, G. Crooks, I. Iakovidis et al., The European Innovation Partnership on Active and Healthy Ageing: The European geriatric medicine introduces the EIP on AHA column, European Geriatric Medicine, vol.5, issue.6, pp.361-363, 2014.
DOI : 10.1016/j.eurger.2014.09.010

J. Bousquet, A. Addis, I. Adcock, I. Agache, A. Agusti et al., Integrated care pathways for airway diseases (AIRWAYS-ICPs), European Respiratory Journal, vol.44, issue.2, pp.304-327, 2014.
DOI : 10.1183/09031936.00014614

J. Bousquet, C. Barbara, E. Bateman, E. Bel, M. Bewick et al., AIRWAYS-ICPs (European Innovation Partnership on Active and Healthy Ageing) from concept to implementation, European Respiratory Journal, vol.47, issue.4, pp.1028-1061, 2016.
DOI : 10.1183/13993003.01856-2015
URL : https://hal.archives-ouvertes.fr/hal-01872376

M. De-planell-saguer, S. Lovinsky-desir, and R. Miller, Epigenetic regulation: The interface between prenatal and early-life exposure and asthma susceptibility, Environmental and Molecular Mutagenesis, vol.8, issue.Suppl 1, pp.231-274, 2014.
DOI : 10.1371/journal.pone.0063812

S. Ho, Environmental epigenetics of asthma: An update, Journal of Allergy and Clinical Immunology, vol.126, issue.3, pp.453-65, 2010.
DOI : 10.1016/j.jaci.2010.07.030

P. Barnes, Targeting the Epigenome in the Treatment of Asthma and Chronic Obstructive Pulmonary Disease, Proceedings of the American Thoracic Society, vol.6, issue.8, pp.693-699, 2009.
DOI : 10.1513/pats.200907-071DP

C. Wu, C. Yang, Y. Chen, C. Chen, L. Chen et al., The DNA Methylation Inhibitor 5-Azacytidine Increases Regulatory T Cells and Alleviates Airway Inflammation in Ovalbumin-Sensitized Mice, International Archives of Allergy and Immunology, vol.53, issue.4, pp.356-64, 2013.
DOI : 10.1016/j.cyto.2010.11.002